Ultrasound-mediated targeted drug delivery with a novel cyclodextrin-based drug carrier by mechanical and thermal mechanisms

TY - JOUR

T1 - Ultrasound-mediated targeted drug delivery with a novel cyclodextrin-based drug carrier by mechanical and thermal mechanisms

AU - Gourevich, Dana

AU - Dogadkin, Osnat

AU - Volovick, Alexander

AU - Wang, Lijun

AU - Gnaim, Jallal

AU - Cochran, Sandy

AU - Melzer, Andreas

N1 - Copyright © 2013 Elsevier B.V. All rights reserved.

PY - 2013/9/28

Y1 - 2013/9/28

N2 - Various mechanisms for ultrasound-mediated targeted drug delivery have been investigated in the past several decades. Cyclodextrins are already known for their ability to encapsulate various drugs in their lipophilic cavity; this paper reports evaluation of the potential of a cyclodextrin-based nanocarrier as a drug delivery vehicle, using cell monolayers in vitro in conjunction with ultrasound as the release mechanism. The application of ultrasound to the cell monolayers results in both thermal and mechanical effects; a current challenge is to differentiate between these effects. In this study, the cell uptake routes of doxorubicin encapsulated in the cyclodextrin-based carrier were investigated, examining individually the thermal and the mechanical effects of focused ultrasound for drug release. Exploiting mechanical effects, the uptake of encapsulated doxorubicin into cancer cells was increased by a factor of up to 5.5 when ultrasound was applied. Thermal application of FUS increased the cellular uptake of encapsulated doxorubicin by a factor of up to 9.6. Hyperthermia without focused ultrasound resulted in an increase by a factor of up to 5.7.

AB - Various mechanisms for ultrasound-mediated targeted drug delivery have been investigated in the past several decades. Cyclodextrins are already known for their ability to encapsulate various drugs in their lipophilic cavity; this paper reports evaluation of the potential of a cyclodextrin-based nanocarrier as a drug delivery vehicle, using cell monolayers in vitro in conjunction with ultrasound as the release mechanism. The application of ultrasound to the cell monolayers results in both thermal and mechanical effects; a current challenge is to differentiate between these effects. In this study, the cell uptake routes of doxorubicin encapsulated in the cyclodextrin-based carrier were investigated, examining individually the thermal and the mechanical effects of focused ultrasound for drug release. Exploiting mechanical effects, the uptake of encapsulated doxorubicin into cancer cells was increased by a factor of up to 5.5 when ultrasound was applied. Thermal application of FUS increased the cellular uptake of encapsulated doxorubicin by a factor of up to 9.6. Hyperthermia without focused ultrasound resulted in an increase by a factor of up to 5.7.

U2 - 10.1016/j.jconrel.2013.05.038

DO - 10.1016/j.jconrel.2013.05.038

M3 - Article

C2 - 23770006

SN - 1873-4995

VL - 170

SP - 316

EP - 324

JO - Journal of Controlled Release

JF - Journal of Controlled Release

IS - 3

ER -